According to general industry estimates about 6 million patients suffer from non-healing wounds per year in the United States. These wounds primarily result from diabetes, immobilization, or circulatory problems. Left untreated, these wounds can lead to infection, amputation, or even death.
The healing of compromised tissues usually progresses through distinct stages leading to the eventual restoration of the natural function. As an example, injury to the skin initiates an immediate vascular response characterized by a transient period of vasoconstriction, followed by a more prolonged period of vasodilation. Blood components infiltrate the wound site, endothelial cells are released, exposing fibrillar collagen, and platelets attach to exposed sites. As platelets become activated, components are released which initiate events of the intrinsic coagulation pathway. At the same time, a complex series of events trigger the inflammatory pathways generating soluble mediators to direct subsequent stages of the healing process. These events may result in a transient to prolonged period of oxygen deprivation known as hypoxia in the tissues.
Normally, the healing process of injured tissues is uneventful and may occur regardless of any intervention. However, where an underlying metabolic condition or perpetual insult such as pressure is a contributing factor, the natural healing process may be retarded or completely arrested, resulting in a chronic wound. Trends in modern medical practices have shown that the wound healing of both acute and chronic wounds may be significantly improved by clinical interventions using methods and materials that optimize conditions in the compromised tissues to support the physiological processes of the progressive stages of tissue repair. In dermal wounds, key factors in providing the optimal conditions are the prevention of dead tissue accumulation and the maintenance of an optimal level of moisture and oxygen in the wound bed. All of these factors may be controlled by the management of wound exudate liquid.
A variety of techniques can be applied to facilitate the natural healing process. For example, wound dressings are commonly applied to wounds to control wound site environmental factors such as water vapor, oxygen permeability, bacterial impermeability, and absorption of exudate. Wound care dressing can be tailored to meet specific requirements including conformability to a body portion, selective adherence to a wound bed, and adhesiveness to the skin surrounding the wound site.
Collagen has been used in many forms as wound dressings such as collagen sponges, as described in Artandi, U.S. Pat. No. 3,157,524 and Berg et al., U.S. Pat. No. 4,320,201. However, most of these dressings are not satisfactory for the various types of compromised tissues. Collagen films and sponges do not readily conform to varied wound shapes. Furthermore, some collagen wound dressings have poor liquid absorption properties and undesirably enhance the pooling of liquids.
Another example of dressings that have been developed is hydrocolloid dressings. UK Patent No. 1,471,013 and Catania et al., U.S. Pat. No. 3,969,498 describe hydrocolloid dressings that are plasma soluble, form an artificial eschar with the moist elements at the wound site, and gradually dissolve to release medicaments. Hydrocolloid dressings in general, and the Catania et al. dressings in particular, are subject to a number of drawbacks. The major disadvantages of these dressings include the potential to disintegrate in the presence of excess liquid at the site, and minimal, virtually negligible, control over water and/or oxygen loss from the wound. This latter disadvantage is particularly important, as excess water loss from a wound will cause an increase in heat loss from the body as a whole, potentially leading to hypermetabolism. In addition, hydrocolloid dressings require frequent dressing changes.
Some types of dressings can cause problems that compromise wound healing. For example, thin film dressings such as those described in U.S. Pat. No. 3,645,835, may maintain excessive moisture over a wound bed, contributing to the overhydration or maceration of surrounding skin. Although sponges and gauze support tissue, they require frequent changing, and cause irritation to the compromised tissues during body movement and dressing removal. Calcium alginates turn into a gelatinous mass during interaction with moisture, are difficult to remove completely, and often dehydrate a wound bed due to the hydrophillic nature of the matrix. In addition, none of these devices or materials contributes to maintaining an appropriate level of oxygen to the compromised tissue site. Nor do any of the currently available devices significantly contribute to or support the autolytic debridement phase of wound healing.
A common problem in the management of both acute and chronic wounds is the maintenance of an optimal level of moisture over the wound bed during heavy exudate drainage. This is usually, but not always, during the early stages of healing. Most moist wound dressing technologies such as thin films, hydrocolloid dressings and hydrogels may be typically overwhelmed by exudate moisture during this heavy drainage phase. Management of moisture during heavy exudate drainage often necessitates the use of gauze or sponge packings that wick away excess moisture from the wound bed, thin film coverings that trap exudate liquid over the wound bed, calcium alginate dressings that chemically bind exudate moisture due to the hydroscopic properties of the seaweed extract and other materials that generally restrict exposure to atmospheric oxygen to the wound site.
The removal of exudate from wounds can be enhanced by negative pressure therapy. Briefly, this system consists of a vacuum arrangement that withdraws undesired material through a porous medium that is placed over the wound. While this approach has been shown to be clinically effective in removing exudate and maintaining a moist, sealed environment it does not address the issue of oxygen delivery or other nutrient requirements present in a sub-dermal wound bed's physiology.
Another common problem in tissue treatment is lack of oxygen or other critical nutrients at the wound site. Specifically, oxygen is the single most powerful aid in wound healing. Unfortunately, damage to tissue and vasculature around the wound site may disrupt circulation and limit oxygen transfer at the location where it is most needed. Hypoxemia, caused by disrupted vasculature, is a key factor that limits wound healing. Measurements have shown that the tissue oxygen tension within the wound and surrounding damaged tissues is substantially lower than the normal blood vascular oxygen tension. Whereas the blood vascular oxygen level of 80 to 100 mm Hg is considered normal, the wound environment may have as little as 3 to 30 mm Hg of oxygen. Research has shown that a level of 30 mm Hg or less is insufficient to support the processes of wound repair. Correcting hypoxemia through the administration of supplemental oxygen (O2) may have significant beneficial impact on wound healing in the perioperative and outpatient settings.
Many approaches have been used in an effort to increase the amount of oxygen delivered to compromised tissues. Initial developments to increase the oxygen tension in the compromised tissue environment involved either topical delivery of oxygen to the tissues or chambers in which the blood vascular oxygen tension is substantially elevated so as to also increase to tissue oxygen levels by diffusion. U.S. Pat. No. 4,328,799 describes a hyperbaric oxygen chamber that was constructed such that it fit tightly to a portion of the anatomy. The chamber was then flooded with oxygen gas to higher than atmospheric pressure to increase dissolution of oxygen for delivery to cellular processes. U.S. Pat. Nos. 4,474,571, 4,624,656, and 4,801,291 further describe various improvements for increasing the atmospheric oxygen concentration over the compromised tissue environment. Although these devices are capable of functionally increasing the oxygen level over a wound site, they suffer from the use of cumbersome apparatus, intermittent delivery of oxygen and poor transfer of oxygen from the oxygen-rich atmosphere to the hypoxic tissues.
Another device, disclosed in U.S. Pat. No. 4,608,041, combined delivery of oxygen to tissues with providing an escape pathway for spent gas and wound-derived volatiles. U.S. Pat. No. 4,969,881 extended this development to use less bulky construction by utilizing an oxygen permeable membrane sandwich in which the interior portion was flooded with oxygen, which diffused through the wound contact membrane, but not the upper membrane, to oxygenate tissues. This was further improved in U.S. Pat. No. 6,000,403. These devices represent improvements that overcame much of the bulky characteristics of previous inventions but represent little or no improvement in the transfer of oxygen to hypoxic tissues nor do they constitute improvements in wound contact matrices customarily needed for wound care.
A different approach, used to increase the efficiency of the transfer of oxygen and to eliminate the bulky apparatus was to use nascent oxygen generation near the device. U.S. Pat. No. 5,407,685 provides a device for generating oxygen when the device was applied to a wound. The device disclosed is a bi-layered device where each layer contains a reactant that mixes and generates oxygen once exudate or other bodily-derived material activates the reaction. U.S. Pat. No. 5,736,582 describes the generation of oxygen from hydrogen peroxide for release at or near the skin surface. U.S. Pat. No. 5,855,570 similarly uses an electrochemical reaction to convert oxygen in air to a peroxide or other reactive form of oxygen for delivery to the wound environment. U.S. Pat. No. 5,792,090 uses a reservoir that contained hydrogen peroxide and a catalyst in a device in contact with the wound, such as a hydrogel or polymeric foam. Another approach was disclosed in U.S. Pat. No. 5,086,620 in which pure gaseous oxygen was dispersed by sonic energy into a liquid matrix that was then solidified by cooling to encapsulate the oxygen in minute bubbles.
These devices represent improvements in the delivery of topical oxygen to the wound environment over the hyperbaric chamber. However, each carries significant limitations that have restricted the broad adaptation of the technology of topical oxygenation for care of compromised tissues. Previously described devices do not have a known concentration of oxygen and cannot function independently of atmospheric pressures or temperature to achieve effective oxygen distribution. In addition, the dependence upon activation by body-derived agents is unpredictable so as to make such devices impractical. Other devices are expensive to produce and require specialized equipment. Such devices cannot be used in the production of cold set polymers that are often used for the construction of medical devices used for compromised tissue care
Another aspect of tissue treatment is the delivery of active agents to the site of the injury. Active agents for use in compromised tissue treatment may be administered to an individual in a variety of ways. For example, active agents may be administered via methods known to those skilled in the art, such as topically, sublingually, orally, or by injection (subcutaneous, intramuscular or intravenous). Nevertheless, there are drawbacks to many of these methods, and an inexpensive, reliable, localized and relatively pain-free method of administering active agents has not been provided in the prior art.
One common method employed for the treatment of compromised tissues is the topical application of a salve or ointment. Topical application to a wound can be painful. Additionally, in the case of a deeply cavitated wound, an excess of active agent may be required because the agent must diffuse through layers of necrotic tissue and newly forming epidermal tissues. Furthermore, application of topical agents to sites in the interior of the body is highly impractical in that the topical agents are washed off or migrate to other sites. This difficulty in delivering the agent may require the application of an excessive amount of the agent and preclude an accurate determination of the effective amount of active agent delivered.
The oral and sublingual administrations of active agents used in tissue treatment also have their drawbacks. Ingestion of an active agent may result in the agent having negative system-wide effects and possibly disturbing the normal flora, or normal microbial environment, whose presence benefits an individual. Successful absorption of the agent into the bloodstream also depends on several factors such as the agent's stability in gastrointestinal liquids, the pH of the gastrointestinal tract, solubility of solid agents, intestinal motility, and gastric emptying.
Injection of an active agent, a normally painful method of administration, may have the same negative system-wide effects as that of an oral or sublingual administration. Yet more importantly, a danger inherent in the injection of an active agent is that rapid removal of the agent is impossible once it is administered. There is also a risk of transmission of infections and the possibility of vascular injury due to the use of needles. Topical, oral, sublingual and intravenous methods of administration pose several problems when delivering active agents for the treatment of compromised tissues.
What is needed therefore, are methods and compositions for improving treatments for compromised tissue comprising materials having superior exudate management capabilities, together with the ability to deliver active therapeutic agents and participate in the management of oxygen tension and other nutrient requirements around such sites. Methods and compositions are needed that can provide oxygen delivery to any size area of compromised tissue and preferably, may also provide moisture control and delivery of other active agents.